Single-cell profiling reveals immune-based mechanisms underlying tumor radiosensitization by a novel Mn porphyrin clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001)
Cite this dataset
Park, Won; Noh, Sun Up; Lim, Jinyeong (2024). Single-cell profiling reveals immune-based mechanisms underlying tumor radiosensitization by a novel Mn porphyrin clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001) [Dataset]. Dryad. https://doi.org/10.5061/dryad.b2rbnzspd
Abstract
Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001, MnBuOE), using single-cell analysis in murine carcinoma model. Mice bearing 4T1 tumors were divided into 4 groups: control, MnBuOE, radiotherapy (RT), combined MnBuOE, and radiotherapy (MnBuOE/RT). In epithelial cells, epithelial-mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT compared to the RT. All subtypes of cancer-associated fibroblasts (CAFs) were reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor-ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT than in the RT. Trajectory analysis showed that DC maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT compared to the RT, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell-cell communications was the lowest in the MnBuOE/RT. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001 from the perspective of each cell type within the tumor microenvironment.
README: Single-cell profiling reveals immune-based mechanisms underlying tumor radiosensitization by a novel Mn porphyrin clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001)
https://doi.org/10.5061/dryad.b2rbnzspd
The dataset comprises filtered matrices generated by CellRanger (barcodes.tsv, features.tsv, matrix.mtx), along with single-cell annotated metadata (Major_cell_annotations.txt), intended for publication in Antioxidants 2024
Descriptions
Single-cell sequencing data
- barcodes.tsv: the barcodes (unique cell-id) saved as TSV format that corresponds to 10x formats
- features.tsv: the features/genes saved as TSV format that corresponds to 10x formats
- matrix.mtx: the matrix files are stored in MTX corresponding to 10x formats.
- Major_cell_annotations.txt: a meta-data file is included that contains the following columns.
- barcodes: Contains unique cell barcodes. The prefix "Bx-Px" is concatenated in front of the barcodes, corresponding to batch names.
- grid.ident: Corresponding sample names.
- Batch: Contains batch names from B1 to B9 to create unique barcode names.
- Sample: Unique sample names, created by concatenating the group and time information (e.g., Group-Time).
- Group: Represents the experimental group, categorized as CN (control), MB (MnBuOE), RT (Radiotherapy), or MR (MnBuOE+RT).
- Time: Indicates the time after irradiation, specified as D10 or D15.
- Cluster1: Annotated cell clusters, divided into 10 major clusters: Macrophages/Monocytes, Neutrophils, T cells, DCs (pDC+cDC), Epithelial cells, Fibroblasts, Endothelial cells, Myocytes, and Stressful-MT.
- Immune: Categorized into immune cells and non-immune cells based on the annotations from Cluster1.
R Scripts for Analysis
- Global_celltype_annotations.R: R script for global cell type annotations analysis.
- Figurex_figure_scripts.R: R scripts for generating manuscript figures. Each script is dedicated to a specific figure (e.g., Figure1_figure_scripts.R, Figure2_figure_scripts.R, etc.).
Funding
Ministry of Science and ICT, Award: NRF-2023R1A2C2003774